Thrombosis refers to the formation of a blood clot within the vascular system. Clot formation is a normal response to hemorrhage and helps to maintain hemostasis. If thrombosis occurs at the wrong place or at the wrong time, it can lead to reduced blood flow to critical organs such as the brain (stroke), lungs (pulmonary embolism), and myocardium (myocardial infarction). Venous thrombosis, which occurs mainly in the deep veins of the leg, often results in pulmonary embolism, when a portion of the clot flows through the circulation to the lungs. Atherothrombosis, or clots that form in arteries, lead to acute coronary syndrome, ischemic stroke, and limb ischemia.
Thrombus formation involves several sequential steps that typically begin following a skin laceration or a vascular injury. Circulating platelets first adhere to the site of injured endothelial cells and a series of events occurs that allows activation of these platelets. Activated platelets then recruit additional platelets to the site of injury, where they aggregate to form a plug until a stable clot forms. Inactive coagulation factors, which are always present and circulating in the bloodstream, are then sequentially activated in a process known as the coagulation cascade. The coagulation cascade ultimately leads to a stable fibrin-containing clot.
Thrombotic disorders are a group of inherited and acquired disorders that cause abnormal activation of the hemostatic system, leading to an increased risk of venous and arterial thrombosis. Cancer is among the acquired disorders that greatly increase the risk of thrombosis. Tumor cells, by expressing high levels of tissue factor on their surface, cause a hypercoagulable state. Tissue factor is required for initiating the just-mentioned coagulation cascade.
Among the factors involved in thrombus formation is protein disulfide isomerase (PDI). PDI is secreted by activated endothelial cells and platelets, after which it plays a critical role in thrombus formation. PDI can activate tissue factor, which leads to activation of the coagulation cascade, ultimately resulting in fibrin deposition and thrombus formation.
It is known that certain natural antioxidants, such as quercetin, inhibit both acute and chronic phases of free-radical induced diseases. Further, some natural antioxidants exhibit synergy in their reactions with biologically relevant oxygen species, e.g., hydroxyl radicals, superoxides, oxysulfurs, sulfur dioxide, and nitrogen dioxide.
Quercetin, in addition to its effects on free-radical induced diseases, is known to inhibit platelet aggregation in vitro. Quercetin administration is also known to reduce blood pressure in hypertensive patients.